Bipolar Brain vs. Non-Bipolar Brain: Key Differences

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Most people probably think of bipolar disorder as a psychiatric disorder, but it is also considered a neurological disorder. This is because the expression of the genes associated with bipolar leads to chemical, structural, and functional neurological differences from a brain that doesn’t have bipolar.

Here’s a look at how the brain of someone with bipolar disorder might differ from someone who doesn’t have bipolar, including people with unipolar depression

Brain Structure

First, let's discuss some background information on the brain in general. It is made up of four lobes, each responsible for governing different brain functions:

  • Frontal lobe: The frontal lobe controls motor skills, personality, and other cognitive functioning.
  • Parietal lobe: Controls vision, hearing, and other sensory functions
  • Temporal lobe: This area helps you understand written and oral language.
  • Occipital lobe: This part of the brain helps control visual interpretation.
  • Gray matter: Consists of neural structures and is the main component of the central nervous system
  • White matter: Consists of myelinated axons and is located below the cortex. White matter contains fewer cell bodies than gray matter.

Structural Differences

Studies have shown reduced gray matter in people with bipolar, and these deficits are most pronounced in the areas of the brain controlling inhibition and motivation—frontal and temporal regions. Those with a history of psychosis do have less gray matter, but if they took lithium or another anti-epileptic/antipsychotic, they showed signs of reversing that.

Bipolar disorder may be considered a neurodegenerative disease, as the longer someone has been dealing with it, the less cortical thickness they showed in frontal, medial parietal and occipital regions.

In a study of people with bipolar disorder and “healthy people,” the most consistent differences were the reduced thickness in both the frontal and temporal cortices (note: there was no difference between bipolar I or bipolar II).

These frontal and temporal lobe differences are partially heritable and traceable to the pathophysiology (how disease affects one physically) of bipolar disorder. Additionally, lifestyle factors such as alcohol use, smoking, and other substance use may affect cortical structure.

Brain Function

Of course, if bipolar disorder is literally changing the brain’s structure, it will also change and affect how it functions. If you have bipolar or know someone who does, you probably know this intuitively, but here’s what that actually looks like. 

  • Bipolar disorder can be a progressive disease, meaning changes in the brain lead to a more severe course of illness as well as neurocognitive deterioration. As a disease/disorder progresses, it leads to less neurogenesis, or fewer neurons developing in the brain. Developing new neurons is important because they help the brain respond to the cognitive load it faces. 

This progression/neurocognitive deterioration may be partly why some people have a progressive course of shortening time between manic or depressive intervals, as well as functional and cognitive impairment, treatment resistance, and suicide attempts. 

  • Changes occur on two levels in bipolar (and other disorders)—state changes and trait changes. State changes are symptoms that one might experience during a manic or depressive episode that are temporary, whereas trait changes are enduring changes that last even in remission/recovery from episodes. An example of a trait marker/change is someone with bipolar disorder still experiencing heightened emotionality in a time or area where one would likely be having neutral or “cold” emotions.

Neurocognitive function deficits are seen in three core domains: 


In one study, patients with bipolar disorder were asked to monitor a stream of stimuli in order to identify a certain one—to measure their ability to hold sustained attention. Patients in states of mania struggled more than patients who were not in a state of mania to complete this test, as well as committing more false alarms, and responding to non-target stimuli.

These are likely analogous to the symptoms of impulsivity and disinhibition in a manic state. 

Executive Function

Executive function refers to a number of psychological processes that allow for organization, planning, and working memory—processes related to the health of the prefrontal cortex. Of any symptom, a lack of executive function may hinder most patients’ abilities to participate in their everyday life—and thus affect their quality of life.

Emotional Processing 

In struggles with executive functioning, it is usually the dorsal and lateral aspects of the prefrontal cortex that are affected; the orbital frontal cortex (which sits at the very front of the brain) is linked to emotional processes such as reward evaluation, risky decision-making, and impulse control.

When this area is damaged, there are typically changes in emotional behavior as well as impaired or impulsive judgment and great difficulty evaluating others’ facial expressions. Tests show a lack of impulse control. However, the study also showed that when in remission, these functions recovered substantially, showing that they are maybe related to the manic state. 

Brain Chemistry 

Though the idea of a “chemical imbalance” may be controversial, what is less controversial is that bipolar disorder certainly affects the brain chemically. Research shows that people with bipolar disorder have a distinct “chemical signature” (set of common levels of certain biomarkers). 

Through this research, they found that there is an upset in the balance of excitatory neurotransmitters (the kind that cause neurons to “fire” and pass along messages to the next cell) and inhibitory neurotransmitters (those which block a message from being passed on further).

However, the research also showed that this signature could be reversed by lithium and valproic acid, two common medications used to treat bipolar. They are thought to work by restoring the balance of these neurotransmitters in the brain.

  • Glutamate is an excitatory neurotransmitter that helps neurons communicate. It is present in upwards of 90% of all synapses in the brain. Its actions at the synapse (communications hub of neurons) can either boost or weaken the communication signal. Too much glutamate, as seen in mania, damages nerve cells and the communications network. In depression, it leads to symptoms such as anhedonia and lethargy.
  • Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that blocks certain brain signals to decrease activity in your nervous system, including the messages that signal fear, anxiety, or stress. In bipolar, GABA levels often may be dysregulated, either appearing too high or too low, but this seems to be an association, not a direct cause of certain symptoms. However, medications used to treat bipolar, such as lithium, regulate this.

Brain-derived neurotrophic factor (BDNF) is a protein that promotes neuron growth/survival/helps establish neuronal connections. BDNF regulates complex cognitive functions in a healthy brain, such as learning and memory. It is usually found in an area of the brain that controls eating, drinking, and body weight.

In people with bipolar disorder, the longer they have had the disorder, the lower their BDNF levels will be. Also, the lower the BDNF levels, the more mood episodes are likely—and it seems that the episodes continually deplete levels and are less likely to be restored in between episodes.

A Word From Verywell

Although bipolar disorder can affect the brain in significant ways, it is treatable (if not curable), and many of the medications prescribed to treat it may mitigate many of the cognitive concerns.

13 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Theodora Blanchfield, AMFT
Theodora Blanchfield is an Associate Marriage and Family Therapist and mental health writer using her experiences to help others. She holds a master's degree in clinical psychology from Antioch University and is a board member of Still I Run, a non-profit for runners raising mental health awareness. Theodora has been published on sites including Women's Health, Bustle, Healthline, and more and quoted in sites including the New York Times, Shape, and Marie Claire.